Is AADAC p.Val71Ile (c.211G>A) pathogenic?

AADAC p.Val71Ile (c.211G>A) is classified Uncertain significance in AADAC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: likely benign (0.0919); Ultra-rare (popmax 0.0111%, eas).

How common is AADAC p.Val71Ile (c.211G>A) in the general population?

AADAC p.Val71Ile (c.211G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about AADAC p.Val71Ile (c.211G>A)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

AADAC p.Val71Ile

c.211G>A · rs1344987591 · VCV3128827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.84
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.68 · regional, not allelic
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,884 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000372% 6/1,613,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,977
European (non-Finnish)	8.48e-05%	1,179,732

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AADAC
Protein: p.Val71Ile
Coding: c.211G>A
MANE Select: NM_001086
dbSNP: rs1344987591
Type: single nucleotide variant
Location: chr3:151817438 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64

Full AADAC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AADAC p.Val71Ala Uncertain significance ★ ⚠ same residue
AADAC p.Ala121Gly Uncertain significance ★ ⚠ same type
AADAC p.Ala16Val Uncertain significance ★ ⚠ same type
AADAC p.Ala319Glu Uncertain significance ★ ⚠ same type
AADAC p.Arg146Ser Uncertain significance ★ ⚠ same type
AADAC p.Arg169Cys Uncertain significance ★ ⚠ same type
AADAC p.Arg169His Uncertain significance ★ ⚠ same type
AADAC p.Arg330Cys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/aadac-p-val71ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown